Comparison of class B scavenger receptors, CD36 and scavenger receptor BI (SR-BI), shows that both receptors mediate high density lipoprotein-cholesteryl ester selective uptake but SR-BI exhibits a unique enhancement of cholesteryl ester uptake

Scavenger receptor BI (SR-BI) mediates the selective uptake of high density lipoprotein (HDL) cholesteryl ester (CE), a process by which HDL CE is tak en into the cell without internalization and degradation of the HDL particl e. The biochemical mechanism by which SR-BI mediates the selective uptake o f HDL CE is poorly understood. Given that CE transfer will occur to some ex tent from HDL to protein-free synthetic membranes, one hypothesis is that t he role of SR-BI is primarily to tether HDL close to the cell surface to fa cilitate CE transfer from the particle to the plasma membrane. In the prese nt study, this hypothesis was tested by comparing the selective uptake of H DL CE mediated by mouse SR-BI (mSR-BI) with that mediated by rat CD36 (rCD3 6), a closely related class B scavenger receptor. Both mSR-BI and rCD36 bin d HDL with high affinity, and both receptors mediate HDL CE selective uptak e. However, SR-BI mediates selective uptake of HDL CE with a 7-fold greater efficiency than rCD36, HDL CE selective uptake mediated by rCD36 is depend ent on HDL binding to the receptor, since a mutation that blocks HDL bindin g also blocks HDL CE selective uptake. These data lead us to hypothesize th at one component of HDL CE selective uptake is the tethering of HDL particl es to the cell surface. To explore the molecular domains responsible for th e greater efficiency of selective uptake by mSR-BI, we compared binding and selective uptake among mSR-BI, scavenger receptor BII, and various chimeri c receptors formed from mSR-BI and rCD36. The results show that the extrace llular domain of mSR-BI is essential for efficient HDL CE uptake, but the C -terminal cytoplasmic tail also has a major influence on the selective upta ke process.